MicroRNA Expression in Human Omental and Subcutaneous Adipose Tissue

MicroRNAs (miRNAs) are small non-coding RNAs, that play important regulatory roles in a variety of biological processes, including development, differentiation, apoptosis, and metabolism. In mammals, miRNAs have been shown to modulate adipocyte differentiation. Therefore, we performed a global miRNA gene expression assay in different fat depots of overweight and obese individuals to investigate whether miRNA expression in human adipose tissue is fat-depot specific and associated with parameters of obesity and glucose metabolism. Paired samples of abdominal subcutaneous (SC) and intraabdominal omental adipose tissue were obtained from fifteen individuals with either normal glucose tolerance (NGT, n = 9) or newly diagnosed type 2 diabetes (T2D, n = 6). Expression of 155 miRNAs was carried out using the TaqMan®MicroRNA Assays Human Panel Early Access Kit (Applied Biosystems, Darmstadt, Germany). We identified expression of 106 (68%) miRNAs in human omental and SC adipose tissue. There was no miRNA exclusively expressed in either fat depot, suggesting common developmental origin of both fat depots. Sixteen miRNAs (4 in NGT, 12 in T2D group) showed a significant fat depot specific expression pattern. We identified significant correlations between the expression of miRNA-17-5p, -132, -99a, -134, 181a, -145, -197 and both adipose tissue morphology and key metabolic parameters, including visceral fat area, HbA1c, fasting plasma glucose, and circulating leptin, adiponectin, interleukin-6. In conclusion, microRNA expression differences may contribute to intrinsic differences between omental and subcutaneous adipose tissue. In addition, human adipose tissue miRNA expression correlates with adipocyte phenotype, parameters of obesity and glucose metabolism.

[1]  Yasushi Okuno,et al.  Global correlation analysis for micro-RNA and mRNA expression profiles in human cell lines , 2008, Journal of Human Genetics.

[2]  D. Hume,et al.  Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity , 2008, PloS one.

[3]  J. George,et al.  MicroRNA‐134 Modulates the Differentiation of Mouse Embryonic Stem Cells, Where It Causes Post‐Transcriptional Attenuation of Nanog and LRH1 , 2008, Stem cells.

[4]  M. Fasshauer,et al.  Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. , 2007, Cell metabolism.

[5]  Yu Liang,et al.  BMC Genomics , 2007 .

[6]  M. Stumvoll,et al.  Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. , 2007, The Journal of clinical endocrinology and metabolism.

[7]  Anton J. Enright,et al.  Prediction of microRNA targets. , 2007, Drug discovery today.

[8]  M. Fasshauer,et al.  Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity , 2006, Diabetes.

[9]  M. Fasshauer,et al.  Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. , 2005, Diabetes.

[10]  Ravi Jain,et al.  MicroRNA-143 Regulates Adipocyte Differentiation* , 2004, Journal of Biological Chemistry.

[11]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[12]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[13]  Gary Ruvkun,et al.  Identification of many microRNAs that copurify with polyribosomes in mammalian neurons , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Bruce A. Hay,et al.  The Drosophila MicroRNA Mir-14 Suppresses Cell Death and Is Required for Normal Fat Metabolism , 2003, Current Biology.

[15]  R. Paschke,et al.  Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or Type II diabetes , 2002, Diabetologia.

[16]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[17]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[18]  Marc Montminy,et al.  Transcriptional regulation by the phosphorylation-dependent factor CREB , 2001, Nature Reviews Molecular Cell Biology.

[19]  B. Wajchenberg Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. , 2000, Endocrine reviews.

[20]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[21]  D. Storm,et al.  Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning , 1998, Nature Neuroscience.

[22]  M. Fantone,et al.  Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus , 1997, Diabetes Care.

[23]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[24]  K J Rothman,et al.  No Adjustments Are Needed for Multiple Comparisons , 1990, Epidemiology.

[25]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[26]  C. Wollheim,et al.  MicroRNAs: 'ribo-regulators' of glucose homeostasis , 2006, Nature Medicine.